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  • Systematic Review
  • Published:

Neurodevelopmental consequences of preterm punctate white matter lesions: a systematic review

Abstract

Objectives

To evaluate punctate white matter lesion (PWML) influence in preterm infants on the long-term neurodevelopmental outcome (NDO).

Methods

PubMed and EMBASE were searched from January 1, 2000, to May 31, 2021. Studies were included in which PWML in preterm infants on MRI around term-equivalent age (TEA) and NDO at ≥12 months were reported. Study and patient characteristics and NDO on motor, cognitive, and behavioral domains were extracted. The quality of studies was assessed using the Cochrane-approved Quality in Prognosis Studies tool.

Results

This analysis included nine studies with a total of 1655 patients. Mean incidence of isolated PWML was 22.1%. All studies showed a relationship between PWML and motor delay. Two studies found a significant correlation between cognitive and behavioral outcomes and PWML. Number and PWML location are related to severity and impairment types.

Limitations

PWML were not always separately described from generalized WMI, only studies with imaging around TEA were included, and studies were heterogenic in design and quality.

Conclusions

PWML is common in preterm infants and predictive of adverse NDO, in particular on motor outcomes and less on cognitive and behavioral outcomes. The type and severity of impairments are related to the number and location of PMWL.

Impact

  • PWML is common in preterm infants and seems predictive of adverse NDO.

  • DWI and SWI MRI sequences are informative because the different patterns suggest a difference in the underlying pathology.

  • The type and severity of impairments are related to the number and location of PMWL.

  • Our review can inform clinicians and parents about the NDO of preterm infants with a diagnosis of PWML.

  • Prospective neuroimaging case–control cohort studies are recommended.

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Fig. 1: T1-weighted coronal MRI brain scan at term-equivalent age of a preterm boy (gestational age at birth 27 weeks and 4 days).
Fig. 2
Fig. 3: Assessment of the risk of bias in individual studies.
Fig. 4

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Data availability

All data generated or analyzed during this review study are included in this published article.

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Acknowledgements

The authors would like to thank “Eu-Brain” non-profit association for the technical support in the editing of the article.

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Contributions

C.A.M.d.B. collected data, carried out the initial analyses, and took the lead in writing the manuscript with support from other authors. S.D.M. collected data, wrote the manuscript with support from other authors, and critically reviewed and revised the manuscript. M.L.T. conceptualized the study, and critically reviewed and revised the manuscript. L.A.R., A.R., M.M., and M.B. critically reviewed and revised the manuscript. A.v.d.H. conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed and revised the manuscript. J.D. conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Jeroen Dudink.

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de Bruijn, C.A.M., Di Michele, S., Tataranno, M.L. et al. Neurodevelopmental consequences of preterm punctate white matter lesions: a systematic review. Pediatr Res 93, 1480–1490 (2023). https://doi.org/10.1038/s41390-022-02232-3

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